Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The influence of elevated concentrations of stress hormones on the concentration of ribosomes and the relative proportion of polyribosomes, reflecting protein synthesis in vivo, in human skeletal muscle was investigated. Healthy volunteers were given a 6 h infusion of adrenaline (n = 8), cortisol (n = 8), a triple-hormone combination of adrenaline, cortisol and glucagon (n = 8), or saline (n = 8). 2. The total ribosome concentration declined by 30.4 +/- 7.2% in the triple-hormone group (P less than 0.01), by 26.9 +/- 8.6% in the cortisol group (P less than 0.05) and by 24.8 +/- 11.2% in the adrenaline group (P less than 0.05). The proportion of polyribosomes to total ribosomes decreased by 8.5 +/- 2.2% in the triple-hormone group (P less than 0.05). 3. During hormone infusion the serum glucose levels were enhanced. The insulin concentrations in serum were elevated in the adrenaline group and the triple-hormone group, but not in the cortisol group. Serum insulin decreased in the control group. 4. The results indicate an effect of the combined stress hormone infusion on the total ribosome concentration as well as on the relative abundance of polyribosomes. The single hormones influenced the total ribosome concentration only. The results suggest a critical role for stress hormones in producing the decline in muscle protein synthesis seen after trauma.
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PMID:Stress hormones given to healthy volunteers alter the concentration and configuration of ribosomes in skeletal muscle, reflecting changes in protein synthesis. 260 67

The metabolic response to injury may be presumed to be adaptive, at least in terms of days to weeks. In the wild state where these patterns developed, the wounded organism has poor access to food and must live off its own stores of nutrients, mainly fat, and tissue proteins, mainly from muscle. In fasting, without injury, the organism conserves protein. In this condition there are reductions in blood glucose and insulin levels and increases in glucagon and fatty acid levels. Insulin-dependent tissues stop using glucose; the liver converts fatty acids to ketone bodies, which increase about 100-fold in the fasting human; and the brain substitutes ketone bodies for more than one half of what would otherwise be an obligatory consumption of 100 to 150 g glucose per day in humans. This substitution spares the amount of muscle protein required for gluconeogenesis in liver and kidney, and net N losses can be reduced to less than 6 g per day. Energy expenditure decreases up to 30%. The fasted, injured subject has additional nutritional requirements. Regeneration of the wound and rapidly proliferating white and red blood cells require a source of amino acids and other nutrients. Synthesis of acute-phase proteins required for host defense also needs amino acids. In addition, the wound, regenerating tissue, and white blood cells require large amounts of glucose for glycolysis. That the wound is poorly vascularized may be the major reason for hyperglycemia, which provides a glucose gradient between plasma and tissue high enough for extraction of sufficient glucose. The wound does not increase net consumption of glucose; rather, lactate returns to the liver to be converted again to glucose. Hyperglycemia due to the wound increases the requirements for gluconeogenesis from muscle protein, however. The high concentrations of counterregulatory hormones, cortisol, epinephrine, and glucagon will minimize glucose utilization by insulin-sensitive tissues, despite high concentrations of both glucose and insulin, but these hormones are not able to prevent suppression of ketone body synthesis in the liver. As a result, the brain continues to derive almost all its energy from oxidation of glucose. Synthesis of this glucose in liver is the biggest consumer of amino acids made available by net degradation of muscle protein. The metabolic response to injury, initiated by afferent nerve impulses and cytokines and mediated by increases in counterregulatory hormones and sympathetic activity, is a well-coordinated, well-regulated process controlled largely by the hypothalamus. Increased consumption of nutrients occurs simultaneously with but is not caused by increase in production.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The effects of injury and sepsis on fuel utilization. 266 81

Protein catabolism following injury is associated with elevated levels of the stress hormones cortisol, glucagon, and the catecholamines. To study the effect of hormonal blockade on catabolic responses to surgery, 16 dogs underwent general anesthesia, a standard abdominal operation, and implantation of aortic and caval catheters. Five received phentolamine and propranolol continuously, at doses which block catecholamine effects. To prevent the rise in both catecholamines and cortisol, 6 received a high epidural anesthetic (T4-S3), started preoperatively and continued for 24 hr. Five dogs served as controls. Hindquarter amino acid flux was measured at 6 and 24 hr post-op. Pre- and post-op skeletal muscle biopsies were analyzed for amino acids. Urinary nitrogen was measured over 24 hr. Urinary nitrogen excretion was unaffected by treatment, but urinary creatinine fell from 0.039 +/- 0.002 g/24 hr X kg for controls to 0.03 +/- 0.002 for the epidural group and 0.031 +/- 0.001 for alpha and beta blockade (P less than 0.05). Hindquarter amino acid nitrogen efflux was decreased from -19.05 +/- 4.06 mumole/min X kg in controls to -8.98 +/- 0.86 in the epidural and -6.89 +/- 1.21 in the alpha- and beta-blockade groups (P less than 0.05). The urinary nitrogen loss, glutamine efflux, and fall in muscle glutamine produced by the operation were not prevented by either form of hormonal blockade, but hindquarter nitrogen efflux was diminished. Hormonal blockade inhibits net skeletal muscle protein catabolism without altering whole-body nitrogen loss. Hormones and other factors must be responsible for the increased ureagenesis that occurs following injury.
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PMID:Hormonal blockade modifies post-traumatic protein catabolism. 286 76

Inhibitor-1 purified from rabbit liver could not be distinguished from the skeletal muscle protein by chromatographic, electrophoretic and immunological criteria. Amino acid sequences comprising 68% of rabbit liver inhibitor-1 were identical to the skeletal muscle protein indicating that they are products of a single gene. Total inhibitor-1 activity in heat-treated rabbit liver extracts was similar to that in skeletal muscle extracts, and the phosphorylation state of inhibitor-1 increased from 14% to 42% in rabbit liver in vivo after an intravenous injection of glucagon. Monospecific antibodies to rabbit skeletal muscle inhibitor-1 recognised a single major protein of identical electrophoretic mobility (26 kDa) in each rabbit tissue examined (skeletal muscle, liver, brain, heart, kidney, uterus and adipose). The antibodies also recognised a single major (30 kDa) protein in the same rat tissues, except liver. The results show that while there are interspecies differences in apparent molecular mass, inhibitor-1 is likely to be the same gene product in each mammalian tissue. Inhibitor-1 was not detected in rat liver, either by activity measurements or immunoblotting, irrespective of the age, sex or strain of the animals. Immunoblotting also failed to detect inhibitor-1 in mouse liver, although it was present in guinea pig, porcine and sheep liver. The absence of inhibitor-1 in rat liver indicates that phosphorylation of this protein cannot underlie the increased phosphorylation of hydroxymethylglutaryl-CoA reductase observed after stimulation by glucagon. Monospecific antibodies to rabbit skeletal muscle inhibitor-2 recognised a 31 kDa protein in each rabbit tissue, and a 33 kDa protein in all rat tissues including liver. The results suggest that inhibitor-2 is the same gene product in each mammalian tissue.
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PMID:Partial structure and hormonal regulation of rabbit liver inhibitor-1; distribution of inhibitor-1 and inhibitor-2 in rabbit and rat tissues. 291 4

The existence of a co-ordinated response to stress of a variety of causes has clearly been established. Basically, this consists of an elevation in energy expenditure and an increased breakdown of skeletal muscle protein. In addition, glucose level in the plasma increases as a result of increased synthesis and decreased uptake of glucose into cells. Release of fatty acid into the plasma is also increased, and an elevation in the proportion of energy derived from oxidation of fatty acids is observed. This response is qualitatively very different from that seen in simple starvation, where a progressive reduction in energy expenditure and a reduction in the synthesis of glucose allows fat to become the major energy-producing substrate and also allows sparing of body protein stores. The mechanisms responsible for this altered pattern of metabolism are probably primarily hormonal in nature, with adrenaline, cortisol and glucagon being the major catabolic stimulants. Some evidence exists, however, for alteration in intracellular pathway metabolism. Within the past decade a new class of mediators of the stress response, the cytokines, has been recognized. These substances are protein products of circulating monocytes and the way in which they integrate into the control of the stress response has not been completely elucidated. At present there is evidence that they can stimulate production of catabolic hormones, and also they may well have direct effects in enhancing protein catabolism in muscle. At present the main method for modification of the stress response remains the provision of energy and amino acid, either intravenously or enterally. In the present state of our knowledge, 30-40 kcal kg-1 day-1 would appear to be adequate for most patients, with half provided as fat. Amino acids 3 g kg-1 day-1 will provide adequate nitrogen. It must be said, however, that the most effective method of modifying the stress response is removal of the source of stress by surgery, antibiotics or other primary therapy.
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PMID:The metabolic and nutritional effects of injury and sepsis. 307 81

The effect of major operative trauma on skeletal muscle metabolism was examined in nine patients receiving a constant infusion of calories (1460 kcal/m2/day) and protein (75 gm of amino acids/m2/day) for 5 days before and 4 days after an operation. Compared with the preoperative state, 72 hours after the operation there was a significant rise in arterial levels of glucagon, cortisol, norepinephrine, and inactive triiodothyronine and a drop in concentrations of insulin, active triiodothyronine, and amino acids. Forearm blood flow increased, as well as the efflux from forearm muscle of lactate, taurine, serine, glycine, valine, methionine, isoleucine, leucine, phenylalanine, lysine, arginine, and total amino acid nitrogen (440%). This loss of muscle protein after trauma is associated with increased muscle proteolysis, as measured by increased urinary 3-methylhistidine excretion (83%), and accounts for increased nitrogen loss (54%) from the body. Increased activity of the sympathetic nervous system is manifested by increased levels of epinephrine and norepinephrine, a relative lack of insulin, and increased levels of glucagon. This hormonal milieu plays an important role in the production of hypoaminoacidemia, increased efflux of amino acids and lactate from muscle, and negative nitrogen balance observed in these traumatized patients.
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PMID:Major operative trauma increases peripheral amino acid release during the steady-state infusion of total parenteral nutrition in man. 308 29

1. Male rats (110-140 g body wt.) were restrained by a standard laboratory technique, by wrapping in a linen towel, and subjected to a constant intravenous infusion of saline (0.15 M-NaCl) for periods of 1 or 6 h. Fractional rates of protein synthesis (ks, %/day) were estimated at the start and at the end of the infusion period, by injection of a large concentration of [3H]phenylalanine. 2. In fed and overnight-fasted rats, restraint and infusion of saline for 1 and 6 h decreased ks in skeletal muscle by 15-20% and 30-35% respectively. Plasma glucose, insulin, glucagon and corticosterone concentrations in restrained and infused rats were not characteristic of immobilization stress. 3. Restrained rats responded to nutrient administration; ks in skeletal muscle increased by 35-40% after infusion of a mixture of amino acids and glucose for 1 or 6 h, as compared with saline-infused rats. 4. Restraint and infusion for 1 or 6 h did not overtly decrease ks and kRNA (protein synthesis per unit of RNA) in hypoxaemia-sensitive tissues, such as heart and liver. Restraint and infusion in an open cage, or in a cloth of open weave, did not decrease ks in muscle after 1 h. Blood gas measurements showed that rats restrained in a linen cloth were hypercapnic and acidotic compared with rats in an open cage. 5. It was concluded that respiratory acidosis, rather than hypoxia, resulting from restraint in a linen cloth decreases muscle protein synthesis.
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PMID:The influence of restraint and infusion on rates of muscle protein synthesis in the rat. Effect of altered respiratory function. 313 2

The physiological control of muscle protein balance has been reviewed. In addition to trauma, fasting and reduced activity have been shown to cause muscle protein loss through changes in synthesis and breakdown. Many of the effects of these states are mediated by alterations in the concentrations of insulin, glucagon, steroids and catecholamines. Branched-chain amino acids also appear to have specific effects in improving protein synthesis. Recently, prostaglandins have been identified as having a central role as mediators in the control of protein metabolism by many hormones and pathological states. Identification of factors which control muscle protein synthesis leads to the possibility that the metabolic response to illness and injury and its attendant muscle protein loss could be open to pharmacological manipulation. Inhibition of prostaglandin synthesis by non-steroidal anti-inflammatory drugs can improve muscle protein turnover, but their clinical usefulness may be limited by side-effects. Hormonal manipulation may offer the possibility of abolishing the metabolic response. For example, inhibition of adrenal secretion in surgical patients by spinal anaesthesia appears to modify many of the metabolic effects of injury. A variety of other treatments have been used to minimize the metabolic derangements of injury. Some of these have considerable potential, but as yet clinical benefits from their use have not been positively identified. It is likely that a pharmacological approach to the nutritional disorders of stress and injury will prove to be of major interest in the future.
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PMID:Regulation of muscle protein turnover: possible implications for modifying the responses to trauma and nutrient intake. 314 8

The effect of glucagon on the rate of muscle protein synthesis was examined in vivo and in the isolated perfused rat hemicorpus. An inhibition of protein synthesis in skeletal muscles from overnight-fasted rats at various plasma concentrations of glucagon was demonstrated in vivo. The plantaris muscle (Type II, fibre-rich) was more sensitive than the soleus (Type I, fibre-rich). Myofibrillar and sarcoplasmic proteins were equally sensitive in vivo. However, protein synthesis in mixed protein and in sarcoplasmic and myofibrillar fractions of the heart was unresponsive to glucagon in vivo. In isolated perfused muscle preparations from fed animals, the addition of glucagon also decreased the synthesis of mixed muscle proteins in gastrocnemius (Type I and II fibres) and plantaris, but not in the soleus. The sarcoplasmic and myofibrillar fractions of the plantaris were also equally affected in vitro. Similar results were observed in vitro with 1-day-starved rats, but the changes were less marked.
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PMID:Inhibition of protein synthesis by glucagon in different rat muscles and protein fractions in vivo and in the perfused rat hemicorpus. 341 42

Infusion of glucagon (0.5 mg/h per 100 g body wt.) into fed rats for 6 h inhibited protein synthesis in skeletal muscle, but not in heart. The order of sensitivity of three muscles was plantaris greater than gastrocnemius greater than soleus. Treatment with glucagon for periods of 1 h or less had no effect. Liver protein synthesis was inhibited by glucagon treatment for 10 min, but stimulated after 6 h. The effect of glucagon on muscle was not secondary to impaired food absorption or to depletion of amino acids by increased gluconeogenesis, since the inhibition of protein synthesis was observed in postabsorptive and amino acid-infused rats. The failure of glucagon to inhibit muscle protein synthesis after 1 h may have been caused by the increase in plasma insulin that occurred at this time, since an inhibition was detected in insulin-treated diabetic rats. The lowest infusion rate that gave a significant decrease in muscle protein synthesis was 6 micrograms/h per 100 g body wt., despite a small increase in plasma insulin. This gave plasma glucagon concentrations in the high pathophysiological range, suggesting that glucagon may be significant in the pathogenesis of muscle wasting in metabolic stresses such as diabetes and starvation.
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PMID:The effect of glucagon administration on protein synthesis in skeletal muscles, heart and liver in vivo. 389 31


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